Monkey Kidney Vero Cells Research Articles

Bioactivity of plants used traditionally in the treatment and management of men’s sexual health

Background: In many African societies, men still rely on the long cultural history of utilising medicinal plants to treat and manage their sexual health.Aim: The study evaluated biological activities of 10 ethnobotanically selected medicinal plants.Setting: These plants are used traditionally to treat and manage men’s sexual health in villages under the Thengwe Tribal Authority, Limpopo province.Methods: Acetone extracts were investigated for their antioxidant activity, anti-inflammatory activity against 15-lipoxygenase, inhibition of nitric oxide production on RAW 264.7 macrophages and antimicrobial activity against Neisseria gonorrhoeae and Candida albicans. Phytochemical analysis was performed by determination of total flavonoid and total phenolic content.Results: All the extracts investigated showed moderate to high content of flavonoids and total phenolic content. Cytotoxicity of the extracts was assessed using the XTT reduction assay against Vero monkey kidney cells. Diospyros mespiliformis extract was less toxic and showed significant antioxidant (IC50 = 8.34 µg/mL), anti-inflammatory (IC50 = 63 µg/mL) and antigonococcal (MIC = 0.39 mg/mL) activities. Extracts from Garcinia livingstonei and Rhoicissus tridentata also exhibited promising bioactivity. While these three extracts seem to inhibit the production of nitric oxide, the rest of the extracts seem to promote its production.Conclusion: The findings of the study revealed that the selected plants possess biological activities directly and indirectly associated with men’s sexual health.Contribution: The investigated plants have potential therapeutic effects and can be used as leads in the development of new pharmaceuticals to manage men’s sexual disorders.

Synthesis, crystal structure, cytotoxicity (MCF-7 and HeLa) and free radical scavenging activity of the hydrazones derived from 2-methylsulfonyl-5-nitrobenzaldehyde

The rising levels of breast and cervical cancers among women have become public health problem with high economic burden globally and more especially in low- and middle-income countries. This necessitates discoving new and potent anticancer drugs with reduced or no side effects. The hydrazones derived from 2-formyl-4-nitrophenyl methanesulfonate were characterized using a combination of spectroscopic and single-crystal X-ray diffraction (XRD) techniques. The compounds were, in turn, evaluated for antigrowth effect in vitro against the human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The presence of a chlorine atom on the para position of the phenylhydrazone moiety of 3b resulted in increased cytotoxicity against the MCF-7 and the HeLa cell lines compared to camptothecin (IC50 = 9.15 ± 0.84 µM and 3.71 ± 0.16 µM, respectively) with IC50 values of 5.64 ± 0.84 µM and 2.40 ± 0.13 µM, respectively. Compounds 2, 3a and 3b were found to exhibit significantly reduced toxicity against the Vero cells compared to the anti-cancer drugs, doxorubicin (IC50 = 0.78 ± 0.04 µM) and nintedanib (IC50 = 0.24 ± 0.02 µM) with the IC50 values of 17.86 ± 1.12, 11.89 ± 1.01 and 24.42 ± 0.70 µM, respectively. The hydrazones 3a and 3b exhibited a strong inhibitory effect against the vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase (IC50 = 5.78 ± 0.039 μM and 5.79 ± 0.053 µM, respectively) compared to the carbaldehyde precursor 2 (IC50 = 8.01 ± 0.052 µM) though less active compared to nintedanib (IC50 = 1.05 ± 0.193 µM). The hydrazone derivatives exhibited significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity compared to ascorbic acid and the parent 2-formyl-4-nitrophenylmethanesulfonate. In silico molecular docking studies revealed the binding potential of the hydrazones at the active site of VEGFR-2 tyrosine kinase and cytochrome c peroxidase.

Enzyme (α-Glucosidase, α-Amylase, PTP1B & VEGFR-2) Inhibition and Cytotoxicity of Fluorinated Benzenesulfonic Ester Derivatives of the 5-Substituted 2-Hydroxy-3-nitroacetophenones.

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a-d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF3 or -OCF3) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness.

Inhibitory activity of Euterpe oleracea Mart. fruit extract in West Nile virus infection

West Nile virus (WNV) is a neurovirulent arbovirus whose epidemic capacity is enhanced by the wide occurrence of competent vectors and susceptible avian amplifying hosts. In this study, we investigated the antiviral potential of Euterpe oleracea Mart. fruit extract (EoFE) in WNV infection of monkey kidney (Vero) cell cultures. A chromatographic authentication of the extract revealed a typical two-peak fingerprint attributable to the major anthocyanins of the fruit. As assessed by plaque assays in Vero cells, the extract showed a significant concentration-dependent antiviral effect when present throughout the infection procedure, reaching a maximum inhibition of 66.8 % at 2 mg/mL without significant cytotoxicity or direct action on virus particles. A time-of-addition assay revealed that this anti-WNV effect was mostly exerted after virus entry, as incubation of Vero cells with EoFE before or during virus addition resulted in a nonsignificant decrease of infection efficiency. These results demonstrated a promising potential of EoFE in inhibiting WNV infection that can be further explored as an antiviral strategy.

Exploring the 3,5-Dibromo-4,6-dimethoxychalcones and Their Flavone Derivatives as Dual α-Glucosidase and α-Amylase Inhibitors with Antioxidant and Anticancer Potential.

The rising levels of type 2 diabetes mellitus (T2DM) and the poor medical effects of the commercially available antidiabetic drugs necessitate the development of potent analogs to treat this multifactorial metabolic disorder. It has been demonstrated that targeting two or more biochemical targets associated with the onset and progression of diabetes along with oxidative stress and/or cancer could be a significant strategy for treating complications related to this metabolic disorder. The 3,5-dibromo-4,6-dimethoxychalcones (2a-f) and the corresponding flavone derivatives (3a-f) were synthesized and characterized using spectroscopic (NMR, HR-MS and FT-IR) techniques. The inhibitory effect of both series of compounds against α-glucosidase and α-amylase was evaluated in vitro through enzymatic assays. Selected compounds were also evaluated for potential to activate or inhibit superoxide dismutase. Compound 3c was selected as a representative model for the flavone series and evaluated spectrophotometrically for potential to coordinate Cu(II) and/or Zn(II) ions implicated in the metal-catalyzed free radical generation. A plausible mechanism for metal-chelation of the test compounds is presented. Furthermore, the most active compounds from each series against the test carbohydrate-hydrolyzing enzymes were selected and evaluated for their antigrowth effect on the human breast (MCF-7) and lung (A549) cancer cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The parent chalcone 2a and flavone derivatives 3a, 3c and 3e exhibited relatively high inhibitory activity against the MCF-7 cells with IC50 values of 4.12 ± 0.55, 8.50 ± 0.82, 5.10 ± 0.61 and 6.96 ± 0.66 μM, respectively. The chalcones 2a and 2c exhibited significant cytotoxicity against the A549 cells with IC50 values of 7.40 ± 0.67 and 9.68 ± 0.80 μM, respectively. Only flavone 3c exhibited relatively strong and comparable cytotoxicity against the MCF-7 and A549 cell lines with IC50 values of 6.96 ± 0.66 and 6.42 ± 0.79 μM, respectively. Both series of compounds exhibited strong activity against the MCF-7 and A549 cell lines compared to the analogous quercetin (IC50 = 35.40 ± 1.78 and 35.38 ± 1.78 μM, respectively) though moderate compared to nintedanib (IC50 = 0.53 ± 0.11 and 0.74 ± 0.15 μM, respectively). The test compounds generally exhibited reduced cytotoxicity against the Vero cells compared to this anticancer drug. Molecular docking revealed strong alignment of the test compounds with the enzyme backbone to engage in hydrogen bonding interaction/s and hydrophobic contacts with the residues in the active sites of α-glucosidase and α-amylase. The test compounds possess favorable drug-likeness properties, supporting their potential as therapeutic candidates against T2DM.

Co/Ni/Cu-NH2BDC MOF@natural Egyptian zeolite ore nanocomposite for calcium ion removal in water softening applications.

Water softening is a treatment process required to remove calcium (Ca(II)) and magnesium (Mg(II)) cations from water streams. Nanocomposites can provide solutions for such multiple challenges and have high performance and low application costs. In this work, a multimetallic cobalt, nickel, and copper 2-aminoterephthalic acid metal-organic framework ((Co/Ni/Cu-NH2BDC) MOF) was synthesized by a simple solvothermal technique. This MOF was supported on an Egyptian natural zeolite ore and was used for the adsorption of Ca(II) ions for water-softening applications. The adsorbent was characterized using Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), N2 adsorption-desorption isotherms, and zeta potential measurements. The adsorption isotherm data for the prepared adsorbent toward Ca(II) were best fit using the Redlich-Peterson model and showed a maximum adsorption capacity of 88.1 mg/g. The adsorption kinetics revealed an equilibrium time of 10 min, which was best fit using the Avrami model. The intermolecular interactions of Ca(II) ions with zeolite and MOF were investigated by Monte Carlo simulations, molecular dynamics simulations, and FTIR and XRD analyses. The adsorption sites in the zeolite structure were oxygen atoms, while those in the MOF structure were amine nitrogen atoms. The Ca(II) ions are coordinated with the solvent molecules in both structures. Finally, the in vitro cytotoxicity of this nanocomposite was assessed, revealing viability levels of 74.57 ± 2.1% and 21 ± 2.79% for Vero and African green monkey kidney and human liver (HepG2) cells, respectively. Cytotoxicity assays help assess the environmental impact of these materials, ensuring that they do not harm aquatic organisms or disrupt ecosystems. Thus, this study demonstrated the valorization of MOF/zeolite as a valuable and industry-ready adsorbent that can appropriate Ca(II) contaminants from aqueous streams.

Sofosbuvir Suppresses the Genome Replication of DENV1 in Human Hepatic Huh7 Cells.

Dengue virus (DENV) causes dengue fever and dengue hemorrhagic fever, and DENV infection kills 20,000 people annually worldwide. Therefore, the development of anti-DENV drugs is urgently needed. Sofosbuvir (SOF) is an effective drug for HCV-related diseases, and its triphosphorylated metabolite inhibits viral RNA synthesis by the RNA-dependent RNA polymerase (RdRp) of HCV. (2'R)-2'-Deoxy-2'-fluoro-2'-methyluridine (FMeU) is the dephosphorylated metabolite produced from SOF. The effects of SOF and FMeU on DENV1 replication were analyzed using two DENV1 replicon-based methods that we previously established. First, a replicon-harboring cell assay showed that DENV1 replicon replication in human hepatic Huh7 cells was decreased by SOF but not by FMeU. Second, a transient replicon assay showed that DENV1 replicon replication in Huh7 cells was decreased by SOF; however, in hamster kidney BHK-21 cells, it was not suppressed by SOF. Additionally, the replicon replication in Huh7 and BHK-21 cells was not affected by FMeU. Moreover, we assessed the effects of SOF on infectious DENV1 production. SOF suppressed infectious DENV1 production in Huh7 cells but not in monkey kidney Vero cells. To examine the substrate recognition of the HCV and DENV1 RdRps, the complex conformation of SOF-containing DENV1 RdRp or HCV RdRp was predicted using AlphaFold 2. These results indicate that SOF may be used as a treatment for DENV1 infection.

Bioguided antiplasmodial isolation of six new labdane-type diterpenoids from the stem bark of Croton sylvaticus Hochst. Ex. Krauss

The CH2Cl2-MeOH (1:1, v/v) extract of Croton sylvaticus stem bark selectively exhibited good antiplasmodial activity during preliminary screening against the multidrug-resistant (Dd2) and chloroquine sensitive (3D7) strains of Plasmodium falciparum with IC50 values of 10.57 and 18.47 μg/mL, respectively. After fractionation, the fractions exhibited moderate to good activity with IC50 values ranging from 4.31 to 25.49 μg/mL. The purification of these fractions led to the isolation of six new labdane-type diterpenoids named sylvacrotonins AF (16), alongside seven known compounds (713). Their structures were determined based on the analysis of their NMR and MS data. The isolated compounds were assessed in vitro for their antiplasmodial activity against Pf3D7 and PfDd2. The new labdane-type diterpenoids showed moderate antiplasmodial activity against the two P. falciparum strains, with compound 6 being the most active, with IC50 values of 11.26 and 21.80 μg/mL against PfDd2 and Pf3D7, respectively. Cytotoxic assays were performed on African green monkey kidney Vero cells to ensure that the obtained activity was specific to the parasites. Interestingly, all the tested extracts, fractions, and isolated compounds showed acceptable selectivity (SI > 10) against both Plasmodium strains, except fractions CSB-E (SI = 3.93) and CSB-C (SI = 9.22) against Pf3D7. Globally, with resistance indexes (RIs) lower than 1, all the tested samples were found to be more active against multidrug-resistant (PfDd2) than sensitive (Pf3D7) strains. Furthermore, all the isolated compounds exhibited cell cytotoxicity in the normal Vero cell line. The results from this study confirm the use of C. sylvaticus in malaria-endemic countries for its management and suggest that further lead-optimization studies on hit compounds could drive to the identification of potential lead molecules for antimalarial control and eradication.

Detection and Genetic Analysis of Songling Virus in Haemaphysalis concinna near the China-North Korea Border

Background: Songling virus (SGLV) is a spherical, enveloped, fragmented, negative-stranded RNA virus belonging to the genus Orthonairovirus in the Nairoviridae family. SGLV is transmitted by ticks and can cause disease in humans. This study identified and characterized SGLV in Haemaphysalis concinna ticks collected in 2023 in the Yanbian Korean Autonomous Prefecture (China) near the China-North Korea border. Methods: A real-time quantitative polymerase chain reaction (RT-qPCR) was used to screen for SGLV nucleic acid in ticks. Baby hamster kidney (BHK-21) and African green monkey kidney (Vero) cells were used to isolate strains of SGLV from nucleic acid-positive samples through three successive passages. Next-generation sequencing and phylogenetics methods were used to characterize the SGLVs. Results: Of the 1659 ticks collected from 6 towns in the Yanbian Korean Autonomous Prefecture near the China-North Korea border, positive SGLV nucleic acid results were identified in 19 H. concinna tick pools from Helong and Longjing towns. This discovery led to the extraction of 17 SGLV genome sequences. Homology analysis that compare the newly discovered L, M, and S segments of SGLV strain HLJ1202 revealed nucleotide similarities ranging from 95.5%–97.1%, 91.9%–98.9%, and 98.3%–99.2%, respectively, and amino acid similarities ranging from 95.7%–97.4%, 97.1%–98.8%, and 98.2%–98.9%, respectively. Six distinct clades, characterized by specific geographic locations and host organisms, were identified on the Maximum Likelihood tree of the L segment. The YB129 and YB150 isolates demonstrated SGLV nucleic acid replication across three successive passages in Vero cells, as evidenced by the decrease in RT-qPCR Ct values. Conclusion: This study marks the initial identification of SGLV in H. concinna within the Yanbian Korean Autonomous Prefecture.

Cisplatin Induces Kidney Cell Death via ROS-dependent MAPK Signaling Pathways by Targeting Peroxiredoxin I and II in African Green Monkey (Chlorocebus aethiops sabaeus) Kidney Cells.

Cisplatin [cis-diamminedichloroplatinum(II), CDDP] is a widely used and effective antitumor drug in clinical settings, notorious for its nephrotoxic side effects. This study investigated the mechanisms of CDDP-induced damage in African green monkey kidney (Vero) cells, with a focus on the role of Peroxiredoxin I (Prx I) and Peroxiredoxin II (Prx II) of the peroxiredoxin (Prx) family, which scavenge reactive oxygen species (ROS). We utilized the Vero cell line derived from African green monkey kidneys and exposed these cells to various concentrations of CDDP. Cell viability, apoptosis, ROS levels, and mitochondrial membrane potential were assessed. CDDP significantly compromised Vero cell viability by elevating both cellular and mitochondrial ROS, which led to increased apoptosis. Pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) effectively reduced CDDP-induced ROS accumulation and subsequent cell apoptosis. Furthermore, CDDP reduced Prx I and Prx II levels in a dose- and time-dependent manner. The inhibition of Prx I and II exacerbated cell death, implicating their role in CDDP-induced accumulation of cellular ROS. Additionally, CDDP enhanced the phosphorylation of MAPKs (p38, ERK, and JNK) without affecting AKT. The inhibition of these pathways significantly attenuated CDDP-induced apoptosis. The study highlights the involvement of Prx proteins in CDDP-induced nephrotoxicity and emphasizes the central role of ROS in cell death mediation. These insights offer promising avenues for developing clinical interventions to mitigate the nephrotoxic effects of CDDP.

Extractives from Artemisia afra with Anti-Bacterial and Anti-Fungal Properties.

Secondary metabolites were isolated using chromatographic techniques after being extracted sequentially from the roots of Artemisia afra using organic solvents such as ethanol, ethyl acetate, dichloromethane, and n-hexane. The isolated compounds were evaluated for anti-fungal, anti-bacterial, and cytotoxicity activities. Spectroscopic techniques, including Nuclear Magnetic Resonance (NMR), Fourier transform infrared (FTIR), and liquid chromatography-mass spectrometry (LC-MS), were used to elucidate the structures of the isolated compounds. The phytochemical investigation of A. afra led to the isolation of eight (A-H) compounds which were identified as 3β-taraxerol (A), 3β-taraxerol acetate (B), dodecyl-p-coumarate (C), ferulic acid (D), scopoletin (E), sitosterol-3-O-β-D-glucopyranoside (F), 3,5-di-O-feruloylquinic acid (G) and Isofraxidin-7-O-β-D-glucopyranoside (H) based on spectroscopic data. Compounds A, B, C, F, G, and H are known but were isolated for the first time from the roots of A. afra. The isolated compounds and extracts from A. afra exhibited good anti-fungal and anti-bacterial activity with dichloromethane and ethyl acetate crude extracts (0.078 mg/mL) and compound E (62.5 µg/mL) showed good activities against Escherichia coli. Compounds C and F also showed good activity against Enterococcus faecalis with minimum inhibitory concentration (MIC) values of 62.5 and 31.25 µg/mL, respectively. Extracts and compounds (A-H) exhibited anti-fungal and anti-bacterial properties and showed no toxicity when tested on Vero monkey kidney (Vero) cells.

Development and evaluation of an inactivated Chikungunya virus vaccine

Background: Chikungunya (CHIK) is a debilitating viral disease that can result in high levels of morbidity and, sometimes, even mortality.It is caused by the chikungunya virus (CHIKV), which belongs to the Togaviridae family. Chikungunya disease is characterized by a triadof symptoms: fever, rash, and joint pain. It is generally treated with painkillers and non-steroidal anti-inflammatory drugs (NSAIDs).Chikungunya is a vaccine-preventable disease and various vaccine platforms are being used, including recombinant protein subunit,live-attenuated, inactivated, viral vector, virus-like particles (VLPs), and nucleic acids (DNA and RNA). Objective: The inactivated (killed)virus platform is one of the safest, as there is no chance of reversion to the wild-type virus. Since this uses a traditional vaccine platform,its efficacy and safety are time-tested. Therefore, the study was aimed at developing an inactivated vaccine against CHIKV. Methods:Chikungunya virus was isolated from 53 sera samples. These were then purified, cloned, and sequenced. The 53 isolates were narroweddown to five CHIKV isolates cultured in African green monkey kidney (Vero) cells. The fastest growing isolate was used as the candidatevaccine. It was inactivated using three chemicals – β-propiolactone (BPL), formaldehyde, and binary ethyleneimine (BEI). These wereformulated with and without Mycobacterium w (Mw) and used for immunization of Balb/c mice to evaluate the immunogenicity ofthese formulations. The neutralizing antibody titers were estimated using the plaque reduction neutralization test with a 50% end-point(PRNT50). Results: Purification, cloning and sequencing of the samples confirmed that these were indeed CHIKV isolates. Cell culture ofthe isolates revealed that five isolates grew better than the rest. The isolate AHD4 grew the fastest and was chosen as the candidatevaccine. It was formulated with BPL, formaldehyde, and BEI, with and without Mw. The six formulations were tested for immunogenicityin eight Balb/c mice in each group. The BEI-inactivated CHIKV formulated with Mw elicited the highest neutralizing antibody response.Conclusion: The BEI-inactivated CHIKV formulated with Mw is the best candidate vaccine that could be taken forward for furtherevaluation in rhesus monkeys

Scaffold fabrication for tissue engineering based on radiation copolymerization of polymer blends: (I) Zein/poly (vinyl butyral) blends

AbstractThe main objective of this work is to fabricate scaffold material for tissue engineering and using Vero (monkey kidney cells)/Paulownia tomentosa cells as model cells. For this objective, copolymer blends of poly(vinyl butyral) (PVB) and Zein, the main constituent, have been fabricated as thin films. Fourier‐transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimeter (DSC), and x‐ray diffraction (XRD) were used to characterize the copolymer blends. The findings showed that Zein component degradation caused the gel fraction percentage to decrease with higher irradiation doses. Zein's thermal characteristics are also decreased by the addition of PVB polymer, but they are improved by irradiation to 10 kGy through promoting phase adhesion and the generation of free radicals at boundary surfaces. Vero (Monkey kidney) cells proliferate more rapidly in the blend Zein/PVB (85/15%) irradiated to 45 kGy than in the unirradiated one. On the other hand, the Paulownia tomentosa cells proliferation was died.Highlights Copolymer blends of Zein and PVB were prepared by gamma irradiation. The copolymers were fabricated as scaffold material for tissue engineering using monkey kidney cells. PVB and Zein copolymer were characterized by FT‐IR, SEM, DSC, and XRD. The Zein/PVB (85/15%)—45 kGy has monkey kidney cells proliferation better than unirradiated one.

Development of an Enhanced High-Yield Influenza Vaccine Backbone in Embryonated Chicken Eggs.

Vaccination is an efficient approach to preventing influenza virus infections. Recently, we developed influenza A and B virus vaccine backbones that increased the yield of several vaccine viruses in Madin-Darby canine kidney (MDCK) and African green monkey kidney (Vero) cells. These vaccine backbones also increased viral replication in embryonated chicken eggs, which are the most frequently used platform for influenza vaccine manufacturing. In this study, to further increase the viral titers in embryonated chicken eggs, we introduced random mutations into the 'internal genes' (i.e., all influenza viral genes except those encoding the hemagglutinin and neuraminidase proteins) of the influenza A virus high-yield virus backbone we developed previously. The randomly mutated viruses were sequentially passaged in embryonated chicken eggs to select variants with increased replicative ability. We identified a candidate that conferred higher influenza virus growth than the high-yield parental virus backbone. Although the observed increases in virus growth may be considered small, they are highly relevant for vaccine manufacturers.

Biofilm reduction, in-vitro cytotoxicity and computational drug-likeness of selected phytochemicals to combat multidrug-resistant bacteria

Multidrug-resistant (MDR) bacteria in biofilms are frequently linked with persistent infections across healthcare settings, due to their virulence factors. Since the post-antibiotic era coerces the quest for novel therapeutics, the use of medicinal plants and their phytochemicals emerges as prospective alternatives for the failing antibiotics. Preliminary screening of untargeted drugs for their drug-likeness and biosafety properties is a necessary step in the advancement of the drug discovery process. Thus, the study aimed to assess the noteworthy phytochemicals with antibacterial potential to reduce the biofilm formation of selected MDR bacteria, evaluate their safe use and drug-likeness properties thereby providing advanced knowledge to contribute to the search for safe, antipathogenic drugs. Three phytochemicals of 1,2,3-benzenetriol, guanosine and phytol revealed significant minimum inhibitory concentrations (MIC) between 0.250 – 0.040 mg/mL against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes. Guanosine and phytol, both revealed noteworthy MIC values of 0.016 and 0.031 mg/mL for S. pyogenes and S. aureus, respectively. Five MDR bacterial pathogens treated with 1,2,3-benzenetriol, guanosine and phytol at a concentration of 0.250 mg/mL reduced anti-adhesion and biofilm development up to 78.88% and 31.82%, respectively. In situ visualisation by scanning electron microscope (SEM) displayed guanosine to significantly disrupt the biofilm structures of S. aureus, S. pyogenes and P. aeruginosa. Atomic force microscope (AFM) detected differences between the topographies of S. aureus, S. pyogenes and P. aeruginosa biofilms treated with guanosine and phytol. Guanosine and phytol showed approximately 100% of cell viability in a dose-dependent manner (0.25 – 0.001 mg/mL) while causing no cell damage on African monkey kidney Vero (epithelial) cells and showed a cytostatic rather than a cytotoxic effect. Drug-likeness in-silico screening revealed that the compounds obeyed Lipinski's rules and have bioavailable scores of 0.55F. Guanosine and phytol showed antivirulent, biosafety and drug-likeness properties with significant pharmacokinetic predictions. This study highlights the significance of phytotherapeutics for the development of novel antipathogenic agents.

Toxicity assessment of bioplastics on brine shrimp (Artemia franciscana) and cell lines

Polylactic acid (PLA) and polybutylene succinate (PBS), are categorized as biodegradable bioplastics that have progressively being utilized as food packaging replacing the obtrusive petroleum plastic. This study aims to evaluate the toxicity of bioplastics and petroleum-based plastic polyethylene (PE) on Artemia franciscana and animal cell lines. Each plastic sample was assessed in its powdered form, and the size distribution of PE, PLA, and PBS microplastic particles was observed by optical microscopy. Additionally, the toxicity of hatching percentage and mortality rate was investigated. The results demonstrated that the percentage of hatching and the mortality rate post treatment with PLA and PBS particles for 24 and 48 h did not significantly alter in comparison to those treated with PE particles. However, the percentage of Artemia hatching reduced post treatment with plastic particles in comparison to the control, as well as the mortality rate increased with a high concentration of plastic particles. The morphology of Artemia after ingesting microplastic particles was obtained using phase contrast inverted microscopy. The accumulation of plastic in the Artemia gut was observed succeeding its exposure to PE, PLA, and PBS particles. In addition, the cytotoxicity of plastics on human keratinocyte (HaCaT), normal human dermal fibroblast (NHDF), and African green monkey kidney (Vero) cell lines were determined by MTT assay. The result exhibited that increasing concentrations of microplastic particles had substantially less toxic to practically nontoxic effect on the cells. The biomolecule profile by synchrotron-IR technique displayed that plastics potentially have more alteration effect in epithelial kidney cells (Vero) than fibroblasts (NHDF) and keratinocytes (HaCaT). Our results demonstrate that PE, PLA, and PBS had toxicity on Artemia following ingestion, in accordance with the concentration and duration tests. Moreover, microplastic particles were nontoxic or harmless to animal cell lines and altered some intracellular biomolecule profiles. These discoveries are essential not only for environmental health risk assessment but also in order to establish recommendations toward safer utilization of bioplastics-based materials for a robust lifestyle.

The Oncolytic herpes simplex virus type-1 (HSV-1) vaccine strain VC2 causes intratumor infiltration of functionally active T cells and inhibition of tumor metastasis and pro-tumor genes VEGF and PDL1 expression in the 4T1/Balb/c mouse model of stage four breast cancer.

Introduction: Oncolytic viruses (OVs) provide new modalities for cancer therapy either alone or in combination with synergistic immunotherapies and/or chemotherapeutics. Engineered Herpes Simplex Virus Type-1 (HSV-1) has shown strong promise for the treatment of various cancers in experimental animal models as well as in human patients, with some virus strains licensed to treat human melanoma and gliomas. In the present study we evaluated the efficacy of mutant HSV-1 (VC2) in a late stage, highly metastatic 4T1 murine syngeneic. Method: VC2 was constructed VC2 using double red recombination technology. For in-vivo efficacy we utilized a late stage 4T1 syngeneic and immunocompetent BALB/cJ mouse model breast cancer model which exhibits efficient metastasis to the lung and other organs. Results: VC2 replicated efficiently in 4T1 cells and in cell culture, achieving titers similar to those in African monkey kidney (Vero) cells. Intra-tumor treatment with VC2 did not appreciably reduce average primary tumor sizes but a significant reduction of lung metastasis was noted in mice treated intratumorally with VC2, but not with ultraviolet-inactivated VC2. This reduction of metastasis was associated with increased T cell infiltration comprised of CD4+ and CD4+CD8+ double-positive T cells. Characterization of purified tumor infiltrating T cells revealed a significant improvement in their proliferation ability compared to controls. In addition, significant T cell infiltration was observed in the metastatic nodules associated with reduction of pro-tumor PD-L1 and VEGF gene transcription. Conclusion: These results show that VC2 therapy can improve anti-tumor response associated with a better control of tumor metastasis. improve T cell responses and reduce pro-tumor biomarker gene transcription. VC2 holds promise for further development as an oncolytic and immunotherapeutic approach to treat breast and other cancers.

Mosquito Larvicidal Activity and Cytotoxicity of the Extracts of Aromatic Plants from Malaysia.

Despite ongoing control efforts, the mosquito population and diseases vectored by them continue to thrive worldwide, causing major health concerns. There has been growing interest in the use of botanicals as alternatives to insecticides due to their widespread insecticidal properties, biodegradability, and adaptability to ecological conditions. In this study, we investigated the larvicidal activity and cytotoxicity effects of solvent extracts from three aromatic plants-Curcuma longa (turmeric), Ocimum americanum (hoary basil), and Petroselinum crispum (parsley)-against Aedes albopictus. Subsequently, we examined the phytochemical composition of the extracts through gas chromatography-mass spectrometry (GC-MS) analysis. Results revealed that the hexane extracts of O. americanum and P. crispum exhibited the greatest larvicidal activity with the lowest median lethal concentration (LC50) values (<30 µg/mL) at 24 h post-treatment, with the former found to be significantly less toxic towards African monkey kidney (Vero) cells. The GC-MS analysis of the said extract indicated the presence of different classes of metabolites, including phenylpropanoids, very long-chain alkanes, fatty acids and their derivatives, and terpenes, with the most abundant component being methyl eugenol (55.28%), most of which, have been documented for their larvicidal activities. These findings provide valuable insights into the potential use and development of bioinsecticides, particularly from O. americanum.

Copper(I)-Thiosemicarbazone Complexes with Dual Anticancer and Antiparasitic Activity.

Four new Cu(I) complexes of the general formula [Cu(PP)(LL)][BF4 ], in which PP is a phosphane ligand (triphenylphosphane or 1,2-bis(diphenylphosphano)ethane (dppe)) and LL is a bioactive thiosemicarbazone ligand (4-(methyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) or 4-(ethyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) were synthesized and fully characterized by classical analytical and spectroscopic methods. The anti-trypanosome and anticancer activities were investigated in vitro on Trypanosoma cruzi and in two human cancer cell lines (ovarian OVCAR3 and prostate PC3). To test the selectivity toward parasites and cancer cells, the cytotoxicity on normal monkey kidney VERO and human dermal fibroblasts HDF cells was also evaluated. The new heteroleptic complexes were more cytotoxic on T. cruzi and chemoresistant prostate PC3 cells than the benchmark drugs nifurtimox and cisplatin. The compounds also showed a high level of cellular internalization by the OVCAR3 cells and, in particular, those containing the dppe phosphane showed activation of the cell death mechanism via apoptosis. On the other hand, the production of reactive oxygen species induced by these complexes was not evident.

Fabrication, Characterization, and Biocompatibility Study of Gelatin-Blended Fibroin Scaffold

This research investigates the biocompatibility of gelatin-blended fibroin scaffold fabricated by freeze-dry process. The morphology showed interconnected spongy spheres and polygons shapes with a pore size of 14.144 ± 11.31 and 19.4822 ± 18.71 micrometers, respectively. The formula ratio of fibroin: gelatin of 8:2 contained more random coil, while the formula ratio of fibroin: gelatin of 7:3 exhibited more β-sheet structure. The result revealed that gelatin influences fibroin conformational transition from random coil to beta, which might result from better hydrophobic characteristics. The surface of the formula ratio of fibroin: gelatin at 8:2 and 7:3 was 125.88 ± 9.85 and 130.07 ± 3.72 degrees, indicating the formula ratio of fibroin: gelatin at 7:3 had more hydrophobicity than the formula ratio of fibroin: gelatin at 8:2. The biocompatibility of scaffolds was determined for both formulas of human keratinocyte (HaCaT) and African green monkey kidney (Vero) cell lines by MTT assay. The formula ratio of fibroin: gelatin at 8:2 with various concentrations of 62.50, 125, 250, 500, and 1,000 µg/mL had cell viability percentages of 96.31, 101.74, 97.81, 104.15, and 103.22%, respectively. The formula ratio of fibroin: gelatin at 7:3 with various concentrations of 62.50, 125, 250, 500, and 1,000 µg/mL had cell viability percentages of 106.38, 104.28, 108.54, 97.42, and 97.65%, respectively. The growth of cell lines showed better performance with the hydrophilic characteristics of the scaffold, and it did not make it toxic to the HaCaT and Vero cell lines. These results demonstrated the possibility of gelatin-blended scaffold as a supporting material for skin tissue engineering, especially for wound healing.