Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i10.397
Macroalgae with innumerable metabolites are predominantly identified as potential organisms in industrial and pharmaceutical applications. Herein, an attempt was made to fabricate zinc oxide nanoparticles (ZnO NPs) using the aqueous extract of red macroalgae Kappaphycus alvarezii and evaluate its anti-tumor and anti-bacterial activities, in vitro. ZnO NPs was prepared via chemical reduction (C-ZnO NPs), for comparative analysis, and co-precipitation method with the extract (B-ZnO NPs). Chemical composition analyses, physical characterization by UV Spectrophotometer, Fourier Transform InfraRed (FTIR) spectroscopy, Energy Dispersive X-Ray Analysis (EDX) and Scanning Electron Microscopy (SEM) and anti-oxidant ability by DPPH assay were performed. Anti-microbial activity of the fabricated nanomaterials was performed against E. coli, Bacillus subtilis and Staphylococcus aureus. Cell toxicity study was carried out using MTT assay upon 3T3 and MCF-7 cell lines. The study resulted that the presence of phenolic content in the algal extract enhanced the biological activities of ZnO NPs at an optimized concentration of 100 mM. Total phenolic content was exa mined to be 83.73 mg gallic acid eq/g and the maximum efficiency of DPPH scavenging was revealed by the concentration of 51.99 mg/mL. Anti-bacterial effect of B-ZnO NPs demonstrated maximum efficiency at the concentrations of 800 µg/mL, 400 µg/mL and 600 µg/mL against Escherichia coli, Bacillus subtilis and Staphylococcus aureus respectively. The cell viability study denoted that the fabricated B-ZnO NPs were non-toxic towards 3T3 while significant cytotoxicity was observed against MCF-7 at an IC50 of 75 µg/mL at 48 h. In conclusion, the B-ZnO NPs was observed to be effective as both bactericidal and anti-cancerous nano-agent and considered further for pharmaceutical applications.
{"title":"Fabrication of phyco-functionalized zinc oxide nanoparticles and their in vitro evaluation against bacteria and cancer cell line","authors":"","doi":"10.56042/ijbb.v60i10.397","DOIUrl":"https://doi.org/10.56042/ijbb.v60i10.397","url":null,"abstract":"Macroalgae with innumerable metabolites are predominantly identified as potential organisms in industrial and pharmaceutical applications. Herein, an attempt was made to fabricate zinc oxide nanoparticles (ZnO NPs) using the aqueous extract of red macroalgae Kappaphycus alvarezii and evaluate its anti-tumor and anti-bacterial activities, in vitro. ZnO NPs was prepared via chemical reduction (C-ZnO NPs), for comparative analysis, and co-precipitation method with the extract (B-ZnO NPs). Chemical composition analyses, physical characterization by UV Spectrophotometer, Fourier Transform InfraRed (FTIR) spectroscopy, Energy Dispersive X-Ray Analysis (EDX) and Scanning Electron Microscopy (SEM) and anti-oxidant ability by DPPH assay were performed. Anti-microbial activity of the fabricated nanomaterials was performed against E. coli, Bacillus subtilis and Staphylococcus aureus. Cell toxicity study was carried out using MTT assay upon 3T3 and MCF-7 cell lines. The study resulted that the presence of phenolic content in the algal extract enhanced the biological activities of ZnO NPs at an optimized concentration of 100 mM. Total phenolic content was exa mined to be 83.73 mg gallic acid eq/g and the maximum efficiency of DPPH scavenging was revealed by the concentration of 51.99 mg/mL. Anti-bacterial effect of B-ZnO NPs demonstrated maximum efficiency at the concentrations of 800 µg/mL, 400 µg/mL and 600 µg/mL against Escherichia coli, Bacillus subtilis and Staphylococcus aureus respectively. The cell viability study denoted that the fabricated B-ZnO NPs were non-toxic towards 3T3 while significant cytotoxicity was observed against MCF-7 at an IC50 of 75 µg/mL at 48 h. In conclusion, the B-ZnO NPs was observed to be effective as both bactericidal and anti-cancerous nano-agent and considered further for pharmaceutical applications.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135799263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i11.6067
Artificial Intelligence (AI) has been widely adopted by pharmaceutical industry to aid rationally drug design and development by fostering the quick delivery of drug targets with optimized structures in spite of huge chemical space of >1060 drug molecules. Tamoxifen, Selective Estrogen Receptor Modulator (SERM), is the drug for breast cancer cell, MCF 7 with many side effects. Tamoxifen may cause side effects like increased bone or tumor pain, pain or reddening around the tumor site, hot flashes, nausea and excessive tiredness etc., Therefore, compound which can resist ER’s bioactivity is considered as an important target for treating breast cancer. In this study, AI based Virtual Screening (VS) method using an efficient Generative Neural Network (GNN) model has been experimented to generate high inhibitory potential hit drug-like inhibitors. Physicochemical, Pharmacokinetic and toxicity analysis are carried out for conforming the sub-selection of drug-likeness of inhibitors. Additionally, Molecular Docking studies with DNA (355D) and protein (3EU7) are performed for the evaluation of binding affinity, prediction of intermolecular interactions and inhibition constant. The docked results of the inhibitor M22 (methyl 2-[(2-benzoylphenyl) carbamoyl] benzoate) has low free energy of binding (-8.61 Kcal/mol and -8.05 Kcal/mol) and low Inhibition constant, Ki, value (0.486 μM and 1.25 μM) as compared to Tamoxifen (-6.7 Kcal/mol & -5.62 Kcal/mol and 12.2 μM & 75.85 μM). Thus, minimum amount of the M22 inhibitor is enough as compared to Tamoxifen and M22 has 3 benzene rings, extended conjugation, amide linkage and huge number of labile electrons which facilitates as a potent drug. This study provides a greenish path to synthesise a potent inhibitor, M22, for further experimental studies rather than preparing number of inhibitors on the atom economy way.
{"title":"Generating a potent inhibitor against MCF7 breast cancer cell through artificial intelligence based virtual screening and molecular docking studies","authors":"","doi":"10.56042/ijbb.v60i11.6067","DOIUrl":"https://doi.org/10.56042/ijbb.v60i11.6067","url":null,"abstract":"Artificial Intelligence (AI) has been widely adopted by pharmaceutical industry to aid rationally drug design and development by fostering the quick delivery of drug targets with optimized structures in spite of huge chemical space of >1060 drug molecules. Tamoxifen, Selective Estrogen Receptor Modulator (SERM), is the drug for breast cancer cell, MCF 7 with many side effects. Tamoxifen may cause side effects like increased bone or tumor pain, pain or reddening around the tumor site, hot flashes, nausea and excessive tiredness etc., Therefore, compound which can resist ER’s bioactivity is considered as an important target for treating breast cancer. In this study, AI based Virtual Screening (VS) method using an efficient Generative Neural Network (GNN) model has been experimented to generate high inhibitory potential hit drug-like inhibitors. Physicochemical, Pharmacokinetic and toxicity analysis are carried out for conforming the sub-selection of drug-likeness of inhibitors. Additionally, Molecular Docking studies with DNA (355D) and protein (3EU7) are performed for the evaluation of binding affinity, prediction of intermolecular interactions and inhibition constant. The docked results of the inhibitor M22 (methyl 2-[(2-benzoylphenyl) carbamoyl] benzoate) has low free energy of binding (-8.61 Kcal/mol and -8.05 Kcal/mol) and low Inhibition constant, Ki, value (0.486 μM and 1.25 μM) as compared to Tamoxifen (-6.7 Kcal/mol & -5.62 Kcal/mol and 12.2 μM & 75.85 μM). Thus, minimum amount of the M22 inhibitor is enough as compared to Tamoxifen and M22 has 3 benzene rings, extended conjugation, amide linkage and huge number of labile electrons which facilitates as a potent drug. This study provides a greenish path to synthesise a potent inhibitor, M22, for further experimental studies rather than preparing number of inhibitors on the atom economy way.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135610225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i11.5393
We have earlier demonstrated that a cellular factor, FUSE binding protein1 (FBP1), physically interacts and effectively suppresses the function of tumor suppressor p53 and promotes persistent HCV replication [Dixit et al. JVI 89:7905, 2015). In the present study, we demonstrate that FBP1 interacts with various naturally occurring p53-isoforms isolated from different cancers that carry large deletions at the N- and C-terminal regions but still have an intact DNA binding domain (DBD). We discovered that FBP1 specifically interacts with the DNA binding domain (DBD) of p53 and its isoforms. We further mapped the FBP1-interaction site and identified a 21-residue-long motif spanning amino acid residues 163-183 in the p53-DBD. We further confirmed that Arg175/Cys176, within this motif, is necessary for FBP1 interaction. Arg175/Cys176, located at the junction of the β4 and H1 helix of the L2 Loop, is required for the DNA binding function of p53. Occupying this site containing Arg175/Cys176 by FBP1 may block the DNA binding function of p53.
{"title":"FUSE binding protein1 interacts with Tumor Suppressor p53 and p53-Isoforms through their DNA Binding domain: Mapping the FBP1 binding site","authors":"","doi":"10.56042/ijbb.v60i11.5393","DOIUrl":"https://doi.org/10.56042/ijbb.v60i11.5393","url":null,"abstract":"We have earlier demonstrated that a cellular factor, FUSE binding protein1 (FBP1), physically interacts and effectively suppresses the function of tumor suppressor p53 and promotes persistent HCV replication [Dixit et al. JVI 89:7905, 2015). In the present study, we demonstrate that FBP1 interacts with various naturally occurring p53-isoforms isolated from different cancers that carry large deletions at the N- and C-terminal regions but still have an intact DNA binding domain (DBD). We discovered that FBP1 specifically interacts with the DNA binding domain (DBD) of p53 and its isoforms. We further mapped the FBP1-interaction site and identified a 21-residue-long motif spanning amino acid residues 163-183 in the p53-DBD. We further confirmed that Arg175/Cys176, within this motif, is necessary for FBP1 interaction. Arg175/Cys176, located at the junction of the β4 and H1 helix of the L2 Loop, is required for the DNA binding function of p53. Occupying this site containing Arg175/Cys176 by FBP1 may block the DNA binding function of p53.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135610477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i9.4162
High risk Human Papillomavirus (HPV) is considered the primary causative agent of cervical cancer, a devastating malady with significant morbidity. In India, cervical cancer is one of the major reasons of cancer mortality among women. Poor treatment outcomes of this disease is a matter of grave concern and hence demands aggressive research efforts towards discovery of more effective therapies. Understanding the intricacies of HPV oncogenesis at the molecular level can facilitate the discovery of promising anti-viral drugs. Our research aims at catering to the need of the time by revealing some of the key molecular mechanisms that contributes to HPV oncogenesis that can be utilized to discover promising anti-cancer molecules. We delineated the oncogenic connections between hADA3 and HPVE6 and illustrated its critical role in cellular transformation. Our work also shows how HPV oncoproteins exploits the cellular SUMO machinery to downregulate hADA3 to induce malignancy. This intrigued us to identify the hot spots of hADA3-E6 interaction and design therapeutic peptides against HPV induced cervical cancer. Present review is an attempt to outline our research on novel mechanisms of HPV pathogenesis and its implication on development of improved cervical cancer therapies.
{"title":"Mechanistic insights into the oncogenic partnership of hADA3 and HPVE6 - paving ways for improved cervical cancer therapy","authors":"","doi":"10.56042/ijbb.v60i9.4162","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4162","url":null,"abstract":"High risk Human Papillomavirus (HPV) is considered the primary causative agent of cervical cancer, a devastating malady with significant morbidity. In India, cervical cancer is one of the major reasons of cancer mortality among women. Poor treatment outcomes of this disease is a matter of grave concern and hence demands aggressive research efforts towards discovery of more effective therapies. Understanding the intricacies of HPV oncogenesis at the molecular level can facilitate the discovery of promising anti-viral drugs. Our research aims at catering to the need of the time by revealing some of the key molecular mechanisms that contributes to HPV oncogenesis that can be utilized to discover promising anti-cancer molecules. We delineated the oncogenic connections between hADA3 and HPVE6 and illustrated its critical role in cellular transformation. Our work also shows how HPV oncoproteins exploits the cellular SUMO machinery to downregulate hADA3 to induce malignancy. This intrigued us to identify the hot spots of hADA3-E6 interaction and design therapeutic peptides against HPV induced cervical cancer. Present review is an attempt to outline our research on novel mechanisms of HPV pathogenesis and its implication on development of improved cervical cancer therapies.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"301 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135496268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i9.4029
β-lactamase hydrolyses amide bond of β-lactam ring. β-lactam antibiotics are the main arsenal in antibiotic regime. High degree of mutation and genetic variation in β-lactamase enzymes have elevated the resistance towards β-lactamase inhibitors. There are 4 classes of β-lactamase, namely Class A, C, and D which are Serine proteases and Class B is the Metallo proteases. The most documented one is TEM, where 4 water molecules (315, 319, 440, 441) play an important role in the binding site. In the present work we have tried to explain the involvement of water molecule with respect to docking behavior with S70 (Serine), E166 (Glutamate) and N170 (Asparagine) along with an important Ω – loop (R161-D179) which allosterically modulate the behavior of the binding site. This will aid us to identify potential candidates as novel antibiotics precisely interacting with the substrate binding site and Ω – loop of β-lactamase and their interaction with these 4 water molecules. We have docked Clavulanic acid (CA), Sulbactam (SB), Tazobactam (TB) with wild (1ZG4) and mutated (1ZG6) TEM in the presence and absence of HOH, which justifies the importance of water molecules playing an important role in the hydrolysis of β-lactam as well as modulating the binding affinity of a potential drug candidate.
{"title":"The role of water molecules and its dynamics to the binding site of β-lactamase enzyme with respect to β-lactamase inhibitor","authors":"","doi":"10.56042/ijbb.v60i9.4029","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.4029","url":null,"abstract":"β-lactamase hydrolyses amide bond of β-lactam ring. β-lactam antibiotics are the main arsenal in antibiotic regime. High degree of mutation and genetic variation in β-lactamase enzymes have elevated the resistance towards β-lactamase inhibitors. There are 4 classes of β-lactamase, namely Class A, C, and D which are Serine proteases and Class B is the Metallo proteases. The most documented one is TEM, where 4 water molecules (315, 319, 440, 441) play an important role in the binding site. In the present work we have tried to explain the involvement of water molecule with respect to docking behavior with S70 (Serine), E166 (Glutamate) and N170 (Asparagine) along with an important Ω – loop (R161-D179) which allosterically modulate the behavior of the binding site. This will aid us to identify potential candidates as novel antibiotics precisely interacting with the substrate binding site and Ω – loop of β-lactamase and their interaction with these 4 water molecules. We have docked Clavulanic acid (CA), Sulbactam (SB), Tazobactam (TB) with wild (1ZG4) and mutated (1ZG6) TEM in the presence and absence of HOH, which justifies the importance of water molecules playing an important role in the hydrolysis of β-lactam as well as modulating the binding affinity of a potential drug candidate.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"95 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135496043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i9.3895
Duchenne muscular dystrophy (DMD) is an X-linked, degenerative disease mainly affecting male children, with progressive weakness of whole-body skeletal muscles and the heart. There is a gradual loss of ambulation, heart weakness, and breathing capacity by late teens. Heart or lung dysfunction causes early death in patients during the second or third decade. Steroid treatment delays disease progression by 2-3 years, albeit with serious side effects. The few FDA-approved gene therapies are mutation-specific and exorbitantly priced. There is an unmet medical need for the children affected with DMD. Interestingly, a previous study showed that single nucleotide change caused Jagged1 overexpression, which resulted in avoidance of early death and ambulatory loss in 1-1.5-year-old golden retriever dogs severely affected with muscular dystrophy. Identifying the pathological processes mitigated by Jagged1 overexpression might help understand the mechanism of this rescue. Hence, we generated DMD knockout in zebrafish, another severe model of DMD with overexpression of the human Jagged1 (JAG1). Pathological aspects like cell death, cell proliferation, cytoplasmic and mitochondrial oxidative stress were compared between dystrophic, rescued, and control groups. Surprisingly, JAG1 increased mitochondrial oxidative stress during rescue, while reducing other pathological processes. Similarly, increased mitochondrial ROS production occurred with Jag1 peptide treatment in in vitro differentiated patient-derived myotubes, suggesting a conserved mechanism involved in the rescue.
{"title":"Mitigation of pathological parameters under Jagged1 influence in DMD knockout zebrafish and patient-derived myoblast cultures","authors":"","doi":"10.56042/ijbb.v60i9.3895","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.3895","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is an X-linked, degenerative disease mainly affecting male children, with progressive weakness of whole-body skeletal muscles and the heart. There is a gradual loss of ambulation, heart weakness, and breathing capacity by late teens. Heart or lung dysfunction causes early death in patients during the second or third decade. Steroid treatment delays disease progression by 2-3 years, albeit with serious side effects. The few FDA-approved gene therapies are mutation-specific and exorbitantly priced. There is an unmet medical need for the children affected with DMD. Interestingly, a previous study showed that single nucleotide change caused Jagged1 overexpression, which resulted in avoidance of early death and ambulatory loss in 1-1.5-year-old golden retriever dogs severely affected with muscular dystrophy. Identifying the pathological processes mitigated by Jagged1 overexpression might help understand the mechanism of this rescue. Hence, we generated DMD knockout in zebrafish, another severe model of DMD with overexpression of the human Jagged1 (JAG1). Pathological aspects like cell death, cell proliferation, cytoplasmic and mitochondrial oxidative stress were compared between dystrophic, rescued, and control groups. Surprisingly, JAG1 increased mitochondrial oxidative stress during rescue, while reducing other pathological processes. Similarly, increased mitochondrial ROS production occurred with Jag1 peptide treatment in in vitro differentiated patient-derived myotubes, suggesting a conserved mechanism involved in the rescue.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"160 47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135496044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i9.3968
Due to an increase in serious infections and a lack of efficient therapies, Klebsiella pneumoniae has recently gained more recognition. The production of carbapenemases is one of the most common strategies by which K. pneumoniae acquire resistance to carbapenems which is considered the last resort of antibiotics. Previously collected isolates from different clinical settings and on the basis of their genetic profile, mainly the absence and presence of single or dual carbapenemases (OXA-181, OXA-232, NDM-1, NDM-5, NDM-5+OXA-181, and NDM-1+OXA-232), mutations in porins, and efflux pumps, seven isolates (M40, M52, M39, J20, M53, M49, and M17B) were selected. Its phenotypic resistance against two carbapenem drugs (ertapenem and meropenem) was checked and we found NDM-5 followed by OXA-181 and NDM-5+OXA-181 carrying isolates showed high MIC values. Further, no significant differences were observed either in the presence of efflux pumps or mutations in porins among isolates. By molecular docking, among single amino acid differences between OXA-181 and OXA-232 and with two amino acids differences between NDM-1 and NDM-5, OXA-232 and NDM-5 showed a higher binding affinity than OXA-181 and NDM-1 with both antibiotics. It is concluded that the presence of specific carbapenemases or combinations of the same can drastically increase MIC values. The presence of NDM-5, and OXA-181, or their combinations is more fatal than NDM-1+OXA-232.
{"title":"Genotypic, phenotypic, and in silico analysis of carbapenem-resistant Klebsiella pneumoniae","authors":"","doi":"10.56042/ijbb.v60i9.3968","DOIUrl":"https://doi.org/10.56042/ijbb.v60i9.3968","url":null,"abstract":"Due to an increase in serious infections and a lack of efficient therapies, Klebsiella pneumoniae has recently gained more recognition. The production of carbapenemases is one of the most common strategies by which K. pneumoniae acquire resistance to carbapenems which is considered the last resort of antibiotics. Previously collected isolates from different clinical settings and on the basis of their genetic profile, mainly the absence and presence of single or dual carbapenemases (OXA-181, OXA-232, NDM-1, NDM-5, NDM-5+OXA-181, and NDM-1+OXA-232), mutations in porins, and efflux pumps, seven isolates (M40, M52, M39, J20, M53, M49, and M17B) were selected. Its phenotypic resistance against two carbapenem drugs (ertapenem and meropenem) was checked and we found NDM-5 followed by OXA-181 and NDM-5+OXA-181 carrying isolates showed high MIC values. Further, no significant differences were observed either in the presence of efflux pumps or mutations in porins among isolates. By molecular docking, among single amino acid differences between OXA-181 and OXA-232 and with two amino acids differences between NDM-1 and NDM-5, OXA-232 and NDM-5 showed a higher binding affinity than OXA-181 and NDM-1 with both antibiotics. It is concluded that the presence of specific carbapenemases or combinations of the same can drastically increase MIC values. The presence of NDM-5, and OXA-181, or their combinations is more fatal than NDM-1+OXA-232.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"192 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135496269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i10.1293
Eleutherine bulbosa (Mill.) Urb. is a medicinal plant which has long been used to treat cancer. E. bulbosa bulb extract (EBBE) has been reported to show cytotoxicity towards several types of human cancer. However, the cytotoxic effect of EBBE towards tongue cancer cells has not been investigated. The present study aimed to evaluate the effects of EBBE towards the viability, apoptosis, and migratory activities of tongue cancer cells. Human oral squamous cell carcinoma (HSC)-3 cells were treated with various concentrations of EBBE for 24 h. The number of viable and apoptotic HSC-3 cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sub-G1 assay, respectively. The migratory activities of HSC-3 cells were assessed using scratch and transwell assay. Sonic hedgehog (SHH) expression was measured using immunoblotting. Upon EBBE treatment, apoptotic HSC-3 cells were significantly higher in a concentration-dependent manner (P <0.05). Meanwhile, viability, migratory activities, and migrated HSC-3 cell number were significantly lower in a concentration-dependent manner (P <0.05). The SHH expression levels in EBBE-treated HSC-3 cells were also lower in a concentration-dependent manner. EBBE reduces HSC-3 cell viability through apoptosis and inhibits its migratory activities by downregulating SHH expression.
{"title":"Eleutherine bulbosa bulb extract induces apoptosis and inhibits cell migration by downregulating Sonic hedgehog in human tongue cancer cells: An in vitro study","authors":"","doi":"10.56042/ijbb.v60i10.1293","DOIUrl":"https://doi.org/10.56042/ijbb.v60i10.1293","url":null,"abstract":"Eleutherine bulbosa (Mill.) Urb. is a medicinal plant which has long been used to treat cancer. E. bulbosa bulb extract (EBBE) has been reported to show cytotoxicity towards several types of human cancer. However, the cytotoxic effect of EBBE towards tongue cancer cells has not been investigated. The present study aimed to evaluate the effects of EBBE towards the viability, apoptosis, and migratory activities of tongue cancer cells. Human oral squamous cell carcinoma (HSC)-3 cells were treated with various concentrations of EBBE for 24 h. The number of viable and apoptotic HSC-3 cells were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sub-G1 assay, respectively. The migratory activities of HSC-3 cells were assessed using scratch and transwell assay. Sonic hedgehog (SHH) expression was measured using immunoblotting. Upon EBBE treatment, apoptotic HSC-3 cells were significantly higher in a concentration-dependent manner (P <0.05). Meanwhile, viability, migratory activities, and migrated HSC-3 cell number were significantly lower in a concentration-dependent manner (P <0.05). The SHH expression levels in EBBE-treated HSC-3 cells were also lower in a concentration-dependent manner. EBBE reduces HSC-3 cell viability through apoptosis and inhibits its migratory activities by downregulating SHH expression.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135799258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i10.2804
In the present study, we aimed to evaluate the cytotoxicity and antitumor effect of alone and combined treatment of curcumin, betanin, and coenzyme Q10 (CoQ10) compounds and nickel oxide (NiO) and iron superoxide (Fe2O3) nanoparticles (NPs) on breast cancer cells in vitro and in vivo. The 4T1 breast cancer cells were exposed to different concentrations of Q10, NiO, and Fe2O3 NPs and the inhibitory concentration (IC50) of NPs and compounds and their effect on cell viability In the present study, we aimed to evaluate the cytotoxicity and antitumor effect of alone and combined treatment of curcumin, betanin, and coenzyme Q10 (CoQ10) compounds and nickel oxide (NiO) and iron superoxide (Fe2O3) nanoparticles (NPs) on breast cancer cells in vitro and in vivo. The 4T1 breast cancer cells were exposed to different concentrations of Q10, NiO, and Fe2O3 NPs and the inhibitory concentration (IC50) of NPs and compounds and their effect on cell viability was evaluated by MTT assay. Apoptosis induction in BALB/c mice after treatment with the IC50 concentration of tested compounds was evaluated by flow cytometry. Gene expression was measured using quantitative real-time polymerase chain reaction (qRT-PCR). The IC50 values for Fe2O3 and NiO NPs were found to be 92.42 µg/mL and 21.49 µg/mL, respectively, and were 0.87 µg/mL, 60.14 µg/mL and 83.47 µg/mL for curcumin, betanin, and CoQ10, respectively. Curcumin was more cytotoxic, whereas Fe2O3 showed lower cytotoxicity than the other compounds in the 4T1 line. All treatments significantly exerted anticancer activity against breast tumors. qRT-PCR analysis revealed that treatment with IC50 concentrations of all alone and combined compounds downregulated the expression of Bcl2 and upregulated Bax in breast tumor. The results revealed a significant reduction in TFAM and MiR-455 expression levels. The combination of aforementioned antitumor agents with Fe2O3 and NiO NPs shows a synergistic impact, as apoptosis induction is boosted by a combination of antitumor agents and NPs, and a higher regulatory impact on gene expression occurs compared with monotherapy.
{"title":"Administration of Curcumin, Betanin, and CoQ10 combined with nickel oxide, iron superoxide nanoparticles show preventive effects in breast cancer: Effect on apoptosis pathway and MiR-455 expression","authors":"","doi":"10.56042/ijbb.v60i10.2804","DOIUrl":"https://doi.org/10.56042/ijbb.v60i10.2804","url":null,"abstract":"In the present study, we aimed to evaluate the cytotoxicity and antitumor effect of alone and combined treatment of curcumin, betanin, and coenzyme Q10 (CoQ10) compounds and nickel oxide (NiO) and iron superoxide (Fe2O3) nanoparticles (NPs) on breast cancer cells in vitro and in vivo. The 4T1 breast cancer cells were exposed to different concentrations of Q10, NiO, and Fe2O3 NPs and the inhibitory concentration (IC50) of NPs and compounds and their effect on cell viability In the present study, we aimed to evaluate the cytotoxicity and antitumor effect of alone and combined treatment of curcumin, betanin, and coenzyme Q10 (CoQ10) compounds and nickel oxide (NiO) and iron superoxide (Fe2O3) nanoparticles (NPs) on breast cancer cells in vitro and in vivo. The 4T1 breast cancer cells were exposed to different concentrations of Q10, NiO, and Fe2O3 NPs and the inhibitory concentration (IC50) of NPs and compounds and their effect on cell viability was evaluated by MTT assay. Apoptosis induction in BALB/c mice after treatment with the IC50 concentration of tested compounds was evaluated by flow cytometry. Gene expression was measured using quantitative real-time polymerase chain reaction (qRT-PCR). The IC50 values for Fe2O3 and NiO NPs were found to be 92.42 µg/mL and 21.49 µg/mL, respectively, and were 0.87 µg/mL, 60.14 µg/mL and 83.47 µg/mL for curcumin, betanin, and CoQ10, respectively. Curcumin was more cytotoxic, whereas Fe2O3 showed lower cytotoxicity than the other compounds in the 4T1 line. All treatments significantly exerted anticancer activity against breast tumors. qRT-PCR analysis revealed that treatment with IC50 concentrations of all alone and combined compounds downregulated the expression of Bcl2 and upregulated Bax in breast tumor. The results revealed a significant reduction in TFAM and MiR-455 expression levels. The combination of aforementioned antitumor agents with Fe2O3 and NiO NPs shows a synergistic impact, as apoptosis induction is boosted by a combination of antitumor agents and NPs, and a higher regulatory impact on gene expression occurs compared with monotherapy.","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"82 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135799267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.56042/ijbb.v60i7.4371
{"title":"A microscopy study to distinguish the ultrastructural changes in the ciliated epithelium, type II pneumocytes, macrophages, and neutrophils of bronchoalveolar fluids after severe SARS-CoV-2 infection","authors":"","doi":"10.56042/ijbb.v60i7.4371","DOIUrl":"https://doi.org/10.56042/ijbb.v60i7.4371","url":null,"abstract":"","PeriodicalId":13281,"journal":{"name":"Indian journal of biochemistry & biophysics","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135828346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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