Corrigendum: In vitro and in vivo evaluation of alginate hydrogel-based wound dressing loaded with green chemistry cerium oxide nanoparticles.

[This corrects the article DOI: 10.3389/fchem.2023.1298808.].

In vitro and in vivo evaluation of alginate hydrogel-based wound dressing loaded with green chemistry cerium oxide nanoparticles.

Interactive wound dressings have displayed promising outcomes in enhancing the wound healing process. This study focuses on creating a nanocomposite wound dressing with interactive and bioactive properties, showcasing potent antioxidant effects. To achieve this, we developed cerium oxide nanoparticles utilizing curcumin as both the reducing and capping agent. Characterization techniques such as SEM, EDX, DLS, Zetasizer, FTIR, and XRD were utilized to analyze the cerium oxide nanoparticles synthesized through a green approach. The image analysis on the obtained TEM images showed that the curcumin-assisted biosynthesized CeO2NPs have a size of 18.8 ± 4.1 nm. The peaks located at 28.1, 32.7, 47.1, 56.0, 58.7, 69.0, and 76.4 correspond to (111), (200), (220), (311), (222), (400), and (331) crystallographic planes. We applied the Debye-Scherrer equation and observed that the approximate crystallite size of the biosynthesized NPs is around 8.2 nm based on the most intensive broad Bragg peak at 28.1°. The cerium oxide nanoparticles synthesized were integrated into an alginate hydrogel matrix, and the microstructure, porosity, and swelling behavior of the resulting wound dressing were assessed. The characterization analyses provided insights into the physical and chemical properties of the green-synthesized cerium oxide nanoparticles and the alginate hydrogel-based wound dressing. In vitro studies demonstrated that the wound dressing based on alginate hydrogel exhibited favorable antioxidant properties and displayed hemocompatibility and biocompatibility. Animal studies conducted on a rat full-thickness skin wound model showed that the alginate hydrogel-based wound dressing effectively accelerated the wound healing process. Overall, these findings suggest that the alginate hydrogel-based wound dressing holds promise as a highly effective material for wound healing applications.

Breaking bad news: a descriptive study of physicians' perspective of Sindh, Pakistan.

OBJECTIVE: To assess the perception and attitude of physicians related to breaking bad news. METHODS: The cross-sectional study was conducted at three teaching hospitals in Karachi and Mirpurkhas, Pakistan, from April 2019 to February 2020, after approval from Hamdard University, Karachi, and comprised physicians of either gender having direct patient contact. Data was collected using a questionnaire based on literature. The questionnaire was pilot-tested before distribution among the subjects. The responses were categorised with respect to age, gender and professional experience. Data was analysed using SPSS 25. RESULTS: Of the 230 subjects, 119(51.7%) were females. The overall mean age was 34.5±8.8 years and mean professional experience was 9.1±8.2 years. Overall, 19(8.3%) subjects believed they had a very good ability to deliver bad news, while 26(11.3%) avoided telling the patient the truth about diagnosis, prognosis and treatment. Age had a significant association with correctly defining breaking bad news (p<0.05). CONCLUSIONS: The skill level related to breaking bad news was found to be deficient.

In-Silico Lead Druggable Compounds Identification against SARS COVID-19 Main Protease Target from In-House, Chembridge and Zinc Databases by Structure-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations.

Pharmacological strategies to lower the viral load among patients suffering from severe diseases were researched in great detail during the SARS-CoV-2 outbreak. The viral protease Mpro (3CLpro) is necessary for viral replication and is among the main therapeutic targets proposed, thus far. To stop the pandemic from spreading, researchers are working to find more effective Mpro inhibitors against SARS-CoV-2. The 33.8 kDa Mpro protease of SARS-CoV-2, being a nonhuman homologue, has the possibility of being utilized as a therapeutic target against coronaviruses. To develop drug-like compounds capable of preventing the replication of SARS-main CoV-2's protease (Mpro), a computer-aided drug design (CADD) approach is extremely viable. Using MOE, structure-based virtual screening (SBVS) of in-house and commercial databases was carried out using SARS-CoV-2 proteins. The most promising hits obtained during virtual screening (VS) were put through molecular docking with the help of MOE. The virtual screening yielded 3/5 hits (in-house database) and 56/66 hits (commercial databases). Finally, 3/5 hits (in-house database), 3/5 hits (ZINC database), and 2/7 hits (ChemBridge database) were chosen as potent lead compounds using various scaffolds due to their considerable binding affinity with Mpro protein. The outcomes of SBVS were then validated using an analysis based on molecular dynamics simulation (MDS). The complexes' stability was tested using MDS and post-MDS. The most promising candidates were found to exhibit a high capacity for fitting into the protein-binding pocket and interacting with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation.

Tumor necrosis factor-alpha, prostaglandin-E2 and interleukin-1ß targeted anti-arthritic potential of fluvoxamine: drug repurposing.

Fluvoxamine, a selective serotonin re uptake inhibitor, is used to treat depression. The aim of present study was to evaluate fluvoxamine in acute (egg albumin-induced inflammation) and chronic inflammatory rat models (formaldehyde and complete Freund's adjuvant (CFA)-induced arthritis). Fluvoxamine showed highly significant (p<0.001) protective effect at dose of 50 mg/kg orally with percentage suppression 21.3% as compared to disease control group in acute model. Likewise, formaldehyde-induced arthritic experiment confirmed the significant (p<0.001) anti-arthritic behavior, showed by fluvoxamine (50 mg/kg orally) throughout the study. Moreover, In CFA-induced model, the higher dose (fluvoxamine 50 mg/kg) exhibited highly significant (p<0.001) decrease in paw thickness and arthritic score with significant increase in weight of animals from 123.8± 1.934 g to 130.2± 1.655 g, significantly decreased the level of RF and CRP to level of 12.0±0.707 and 11.40±0.50 respectively and restoration of SOD, CAT (69.8±1.5, 72.0±1.4 respectively). Furthermore, the level of TNF-α, PGE2, and IL-1ß (147.0±2.0, 406.8±2.5, and 93.8±1.3 respectively) in arthritic animals was reduced to significant (p<0.001) level (53.8±1.3, 205±3.6, and 42.0±1.4 respectively) after treatment with fluvoxamine. Furthermore, molecular docking of fluvoxamine against TNF-α, PGE2, and IL-1ß protein targets showed good binding energies which hereby from computational studies proves our compound anti-inflammatory potential. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies reveled that fluvoxamine has very good pharmacokinetic profile with no specific hepatic toxicity and good absorption level. In addition, the skin sensitization test in vitro human cell line activation test (h-CLAT) and KeratinoSens have revealed that isolated flavone is not skin sensitive with confidence score of 59.6% and 91.6%. The current findings validated the anti-arthritic potential of fluvoxamine but it should be recommended for clinical investigation in future research.

Metals-triggered compound CDPDP exhibits anti-arthritic behavior by downregulating the inflammatory cytokines, and modulating the oxidative storm in mice models with extensive ADMET, docking and simulation studies.

Triggering through abiotic stress, including chemical triggers like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metal Nickel on actinobacteria Streptomyces sp. SH-1327 to obtain a stress-derived compound was firstly investigated. A new compound cyclo-(D)-Pro-(D)-Phe (CDPDP) was triggered from the actinobacteria strain SH-1327 with the addition of nickel ions 1 mM. The stress compound was further evaluated for its anti-oxidant, analgesic, and anti-inflammatory activity against rheumatoid arthritis through in-vitro and in-vivo assays in albino mice. A remarkable in-vitro anti-oxidant potential of CDPDP was recorded with the IC50 value of 30.06 ± 5.11 µg/ml in DPPH, IC50 of 18.98 ± 2.91 against NO free radicals, the IC50 value of 27.15 ± 3.12 against scavenging ability and IC50 value of 28.40 ± 3.14 µg/ml for iron chelation capacity. Downregulation of pro-inflammatory mediators (NO and MDA), suppressed levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-Iß) and upregulation of expressions of anti-oxidant enzymes (GSH, catalase, and GST) unveiled its anti-inflammatory potential. CDPDP was analyzed in human chondrocyte cell line CHON-001 and the results demonstrated that CDPDP significantly increased cell survival, and inhibited apoptosis of IL-1ß treated chondrocytes and IL-1ß induced matrix degrading markers. In addition, to evaluate the mitochondrial fitness of CHON-001 cells, CDPDP significantly upregulated pgc1-α, the master regulator of mitochondrial biogenesis, indicating that CDPDP provides protective effects in CHON-001 cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of the CDPDP showed that CDPDP is safe in cases of hepatotoxicity, cardiotoxicity, and cytochrome inhibition. Furthermore, docking results showed good binding of CDPDP with IL-6-17.4 kcal/mol, and the simulation studies proved the stability between ligand and protein. Therefore, the findings of the current study prospect CDPDP as a potent anti-oxidant and a plausible anti-arthritic agent with a strong pharmacokinetic and pharmacological profile.

Integrated Bioinformatics-Based Subtractive Genomics Approach to Decipher the Therapeutic Drug Target and Its Possible Intervention against Brucellosis.

Brucella suis, one of the causative agents of brucellosis, is Gram-negative intracellular bacteria that may be found all over the globe and it is a significant facultative zoonotic pathogen found in livestock. It may adapt to a phagocytic environment, reproduce, and develop resistance to harmful environments inside host cells, which is a crucial part of the Brucella life cycle making it a worldwide menace. The molecular underpinnings of Brucella pathogenicity have been substantially elucidated due to comprehensive methods such as proteomics. Therefore, we aim to explore the complete Brucella suis proteome to prioritize the novel proteins as drug targets via subtractive proteo-genomics analysis, an effort to conjecture the existence of distinct pathways in the development of brucellosis. Consequently, 38 unique metabolic pathways having 503 proteins were observed while among these 503 proteins, the non-homologs (n = 421), essential (n = 350), drug-like (n = 114), virulence (n = 45), resistance (n = 42), and unique to pathogen proteins were retrieved from Brucella suis. The applied subsequent hierarchical shortlisting resulted in a protein, i.e., isocitrate lyase, that may act as potential drug target, which was finalized after the extensive literature survey. The interacting partners for these shortlisted drug targets were identified through the STRING database. Moreover, structure-based studies were also performed on isocitrate lyase to further analyze its function. For that purpose, ~18,000 ZINC compounds were screened to identify new potent drug candidates against isocitrate lyase for brucellosis. It resulted in the shortlisting of six compounds, i.e., ZINC95543764, ZINC02688148, ZINC20115475, ZINC04232055, ZINC04231816, and ZINC04259566 that potentially inhibit isocitrate lyase. However, the ADMET profiling showed that all compounds fulfill ADMET properties except for ZINC20115475 showing positive Ames activity; whereas, ZINC02688148, ZINC04259566, ZINC04232055, and ZINC04231816 showed hepatoxicity while all compounds were observed to have no skin sensitization. In light of these parameters, we recommend ZINC95543764 compound for further experimental studies. According to the present research, which uses subtractive genomics, proteins that might serve as therapeutic targets and potential lead options for eradicating brucellosis have been narrowed down.

Isoprenaline and salbutamol inhibit pyroptosis and promote mitochondrial biogenesis in arthritic chondrocytes by downregulating ß-arrestin and GRK2.

Rheumatoid arthritis and osteoarthritis overlap many molecular mechanisms of cartilage destruction. Wear and tear in cartilage is chondrocyte-mediated, where chondrocytes act both as effector and target cells. In current study, role of ß2-AR was studied in chondrocytes both in vitro and in vivo. High grade inflammation in vitro and in vivo disease models led to decline in anti-inflammatory ß2-AR signaling and use of ß2-AR agonist attenuated arthritis symptoms. Detailed analysis in chondrocytes revealed that Isoprenaline (ISO) and Salbutamol (SBT) increased cell viability and relative Bcl-2 expression, meanwhile, decreased proteins levels of TNF-α, IL-6 and IL-8 in arthritic chondrocytes when compared with control, respectively. SBT preserved physiological concentration of antioxidant enzymes (CAT, POD, SOD and GSH) in cartilage homogenates and ISO inhibited IL-1ß-mediated genotoxicity in arthritic chondrocytes. Moreover, ß2-AR agonist increased mitochondrial biogenesis and proteoglycan biosynthesis by upregulating the gene expression of PGC1-α, NRF2 and COL2A1, Acan, respectively. ISO and SBT inhibited extracellular matrix (ECM) degradation by downregulating the gene expression of MMP1, MMP3, MMP9 and ADAMTS5 in vitro and in vivo study. In mechanism, ß2-AR agonists decreased ß-arrestin and GRK2 pathway, and as a result mice receiving SBT did not exhibit severe disease. Hence our data suggest ß2-AR agonist administered at disease onset can inhibit receptor internalization by downregulating the expression of ß-arrestin and GRK2 in chondrocytes.

Genome-wide Meta-analysis Reveals New Gene Signatures and Potential Drug Targets of Hypertension.

The prevalence of hypertension reported around the world is increasing and is an important public health challenge. This study was designed to explore the disease's genetic variations and to identify new hypertension-related genes and target proteins. We analyzed 22 publicly available Affymetrix cDNA datasets of hypertension using an integrated system-level framework involving differential expression genetic (DEG) analysis, data mining, gene enrichment, protein-protein interaction, microRNA analysis, toxicogenomics, gene regulation, molecular docking, and simulation studies. We found potential DEGs after screening out the extracellular proteins. We studied the functional role of seven shortlisted DEGs (ADM, EDN1, ANGPTL4, NFIL3, MSR1, CEBPD, and USP8) in hypertension after disease gene curation analysis. The expression profiling and cluster analysis showed significant variations and enriched GO terms. hsa-miR-365a-3p, hsa-miR-2052, hsa-miR-3065-3p, hsa-miR-603, hsa-miR-7113-3p, hsa-miR-3923, and hsa-miR-524-5p were identified as hypertension-associated miRNA targets for each gene using computational algorithms. We found functional interactions of source DEGs with target and important gene signatures including EGFR, AGT, AVP, APOE, RHOA, SRC, APOB, STAT3, UBC, LPL, APOA1, and AKT1 associated with the disease. These DEGs are mainly involved in fatty acid metabolism, myometrial pathways, MAPK, and G-alpha signaling pathways linked with hypertension pathogenesis. We predicted significantly disordered regions of 71.2, 48.8, and 45.4% representing the mutation in the sequence of NFIL3, USP8, and ADM, respectively. Regulation of gene expression was performed to find upregulated genes. Molecular docking analysis was used to evaluate Food and Drug Administration-approved medicines against the four DEGs that were overexpressed. For each elevated target protein, the three best drug candidates were chosen. Furthermore, molecular dynamics (MD) simulation using the target's active sites for 100 ns was used to validate these 12 complexes after docking. This investigation establishes the worth of systems genetics for finding four possible genes as potential drug targets for hypertension. These network-based approaches are significant for finding genetic variant data, which will advance the understanding of how to hasten the identification of drug targets and improve the understanding regarding the treatment of hypertension.

Ferroptosis: A New Road towards Cancer Management.

Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management.

A Comprehensive Review of Biological Roles and Interactions of Cullin-5 Protein.

Ubiquitination is a modification of proteins that has a powerful impact on protein function along with other cellular functions. This reaction is regulated through major enzymes, including E3 ligase as a chief enzyme. The Cullin-5 ubiquitin ligase (Cul5) possesses a variety of substrates that maintain the process of ubiquitination as well as proteasomal degradation. It regulates cell development, proliferation, and other physiological tasks in the human body. Moreover, it has been discovered that the expression of Cul5 plays a significant role in specific cancer cells while affecting the progression of tumor cells. This review is based on current knowledge about Cul5 and its expression, signaling pathways, regulation, virus-related responses, and inhibitors for therapeutic strategies.

A Comprehensive In Silico Exploration of Pharmacological Properties, Bioactivities, Molecular Docking, and Anticancer Potential of Vieloplain F from Xylopia vielana Targeting B-Raf Kinase.

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with -11.8 kcal/mol energy than control vemurafenib -10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme's active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era.

Assessment of empagliflozin add-on therapy to metformin and glimepiride in patients with inadequately controlled type-2 diabetes mellitus.

Diabetes mellitus is a multifaceted metabolic disorder, which often required frequent blood glucose monitoring, poly-pharmacy and timely adjustments for its management. The present study focuses to check the effectiveness of empagliflozin add-on therapy in diabetic patients already taking metformin and glimepiride. This was observational, comparative and follow-up cohort study, conducted in a tertiary care hospital of Pakistan. Ninety subjects were enrolled and evenly distributed in Group A (patients on oral therapy of Metformin & Glimepiride) and Group B (patients on oral therapy of metformin, glimepiride and empagliflozin) randomly. The results showed that the addition of empagliflozin to metformin and glimepiride standard therapy provided better control over blood sugar with a significant decrease in HbA1c (16.1% decrease in HbA1c for Group B patients against 8.2% in Group A patients), FBS (23.8% decrease as compared to 14.6% decrease) and BMI (1.5% decrease in Group B patients against 0.06% increase in Group A). The addition of empagliflozin did not exacerbate the toxicity of the existing regimen and is safe to be included in multiple drug regimens. Empagliflozin addition to standard antidiabetic therapy might possess beneficial impacts in managing poorly controlled Type-2 Diabetes Mellitus in the Pakistani population.

Computational Exploration of Anti-Cancer Potential of GUAIANE Dimers from Xylopia vielana by Targeting B-Raf Kinase Using Chemo-Informatics, Molecular Docking, and MD Simulation Studies.

BACKGROUND: Natural products from herbs are abundant and display powerful anti-cancer activities. OBJECTIVES: In the current study, B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma, was tested against two guaiane-type sesquiterpene dimers, xylopin E-F, obtained from Xylopia vielana. METHODS: In this work, a systematic in silico study using ADMET analysis, bioactivity score forecasts, and molecular docking along with its simulations was conducted to understand compounds' pharmacological properties. RESULTS: During ADMET predictions of both the compounds, xylopin E-F displayed a safer profile in hepatotoxicity and cytochrome inhibition, and only xylopin F was shown to be non-cardiotoxic compared to the FDA-approved drug vemurafenib. Both the compounds were proceeded to molecular docking experiments using Autodock docking software, and both the compounds, xylopin E-F, displayed higher binding potential with -11.5Kcal/mol energy compared to control vemurafenib (-10.2 Kcal/mol). All the compounds were further evaluated for their MD simulations, and their molecular interactions with the B-Raf kinase complex displayed precise interactions with the active gorge of the enzyme by hydrogen bonding. CONCLUSION: Overall, xylopin F had a better profile relative to xylopin E and vemurafenib, and these findings indicated that this bio-molecule could be used as an anti-melanoma agent and as a possible anti-cancer drug in the future. Therefore, this is a systematically optimized in silico approach for creating an anti-cancer pathway for guaiane dimers against the backdrop of its potential for future drug development.

Stress Driven Discovery of Natural Products From Actinobacteria with Anti-Oxidant and Cytotoxic Activities Including Docking and ADMET Properties.

Elicitation through abiotic stress, including chemical elicitors like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metals on actinobacteria Streptomyces sp. SH-1312 for secondary metabolite production, with strong pharmacological activity, along with pharmacokinetics profile, was firstly investigated. The optimum metal stress conditions consisted of actinobacteria strain Streptomyces sp. SH-1312 with addition of mix metals (Co2+ + Zn2+) ions at 0.5 mM in Gause's medium. Under these conditions, the stress metabolite anhydromevalonolactone (MVL) was produced, which was absent in the normal culture of strain and other metals combinations. Furthermore, the stress metabolite was also evaluated for its anti-oxidant and cytotoxic activities. The compound exhibited remarkable anti-oxidant activities, recording the IC50 value of 19.65 ± 5.7 µg/mL in DPPH, IC50 of 15.49 ± 4.8 against NO free radicals, the IC50 value of 19.65 ± 5.22 µg/mL against scavenging ability, and IC50 value of 19.38 ± 7.11 µg/mL for iron chelation capacity and the cytotoxic activities against PC3 cell lines were recorded with IC50 values of 35.81 ± 4.2 µg/mL after 24 h, 23.29 ± 3.8 µg/mL at 48 h, and 16.25 ± 6.5 µg/mL after 72 h. Further mechanistic studies have revealed that the compound MVL has shown its pharmacological efficacy by upregulation of P53 and BAX while downregulation of BCL-2 expression, indicating that MVL is following apoptosis in varying degrees. To better understand the pharmacological properties of MVL, in this work, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) were also evaluated. During ADMET predictions, MVL has displayed a safer profile in case of hepatotoxicity, cytochrome inhibition and also displayed as non-cardiotoxic. The compound MVL showed good binding energy in the molecular docking studies, and the results revealed that MVL bind in the active region of the target protein of P53 and BAX. This work triumphantly announced a prodigious effect of heavy metals on actinobacteria with fringe benefits as a key tool of MVL production with a strong pharmacological and pharmacokinetic profile.

Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review.

Although the rates of many cancers are controlled in Western countries, those of some cancers, such as lung, breast, and colorectal cancer are currently increasing in many low- and middle-income countries due to increases in risk factors caused by development and societal problems. Additionally, endogenous factors, such as inherited mutations, steroid hormones, insulin, and insulin-like growth factor systems, inflammation, oxidative stress, and exogenous factors (including tobacco, alcohol, infectious agents, and radiation), are believed to compromise cell functions and lead to carcinogenesis. Chemotherapy, surgery, radiation therapy, hormone therapy, and targeted therapies are some examples of the approaches used for cancer treatment. However, various short- and long-term side effects can also considerably impact patient prognosis based on clinical factors associated with treatments. Recently, increasing numbers of studies have been conducted to identify novel therapeutic agents from natural products, among which plant-derived bioactive compounds have been increasingly studied. Naringin (NG) and its aglycone naringenin (NGE) are abundantly present in citrus fruits, such as grapefruits and oranges. Their anti-carcinogenic activities have been shown to be exerted through several cell signal transduction pathways. Recently, different pharmacological strategies based on combination therapy, involving NG and NGE with the current anti-cancer agents have shown prodigious synergistic effects when compared to monotherapy. Besides, NG and NGE have been reported to overcome multidrug resistance, resulting from different defensive mechanisms in cancer, which is one of the major obstacles of clinical treatment. Thus, we comprehensively reviewed the inhibitory effects of NG and NGE on several types of cancers through different signal transduction pathways, the roles on sensitizing with the current anticancer medicines, and the efficacy of the cancer combination therapy.

Antimicrobial potential of aqueous extract of Camellia sinensis against representative microbes.

Camellia sinensis is being used for decades for its therapeutic efficacies against physiological problems and microbial infections. This study was undertaken to investigate the antibacterial and antifungal potential of aqueous extract of Camellia sinensis. Antibacterial activity was determined by disc and well diffusion assay. MIC and MBC were calculated by broth dilution method. Miles and Misra technique was used to find out colony forming unit per/ml. All the test organisms revealed a diverse range of vulnerability against aqueous extract. Among Gram positive, MRSA showed to be the most sensitive with least MIC and MBC while among Gram-negative Pseudomonas aeruginosa exhibited the highest sensitivity. In Miles and Misra, a progressive decline in log of CFU/ml was observed. In time-kill assay, a decline was noted in the viable count of S.aureus after exposure to 18% aqueous extract of Camellia sinensis. In the present study aqueous extract of Camellia sinensis found to be effective against Gram positive, Gram negative and fungi. The most important finding of this study is its aqueous extract inhibitory effect against drug-resistant microorganisms e.g. MRSA and P. aeruginosa and Candida albicans.

Current status and future therapeutic perspectives of glioblastoma multiforme (GBM) therapy: A review.

Glioblastoma multiforme (GBM) is the deadliest form of heterogeneous brain cancer. It affects an enormous number of patients every year and the survival is approximately 8 to 15 months. GBM has driven by complex signaling pathways and considered as a most challenging to treat. Standard treatment of GBM includes surgery, radiation therapy, chemotherapy and also the combined treatment. This review article described inter and intra- tumor heterogeneity of GMB. In addition, recent chemotherapeutic agents, with their mechanism of action have been defined. FDA-approved drugs also been focused over here and most importantly highlighting some natural and synthetic and novel anti- glioma agents, that are the main focus of researchers nowadays.

Emerging biopharmaceuticals from bioactive peptides derived from marine organisms.

Biologically active natural products are spontaneous medicinal entrants, which encourage synthetic access for enhancing and supporting drug discovery and development. Marine bioactive peptides are considered as a rich source of natural products that may provide long-term health, in addition to many prophylactic and curative medicinal drug treatments. The large literature concerning marine peptides has been collected, which shows high potential of nutraceutical and therapeutic efficacy encompassing wide spectra of bioactivities against a number of infection-causing agents. Their antimicrobial, antimalarial, antitumor, antiviral, and cardioprotective actions have achieved the attention of the pharmaceutical industry toward new design of drug formulations, for treatment and prevention of several infections. However, the mechanism of action of many peptide molecules has been still untapped. So in this regard, this paper reviews several peptide compounds by which they interfere with human pathogenesis. This knowledge is one of the key tools to be understood especially for the biotransformation of biomolecules into targeted medicines. The fact that different diseases have the capability to fight at different sites inside the body can lead to a new wave of increasing the chances to produce targeted medicines.